AUTISM CONNECT DIRECTORY

Stem cell therapy is the latest scientific breakthrough in the medical treatment of autism. Whereas on one hand, stem cell therapy brings a lot of hope to children with autism, there is also a lot of hype. Therefore, the optimism of stem cell therapy needs to be considered with caution before we make any final decision in this connection.

On one hand, many centers all the over the world claim to have treated children with autism, with a good safety record and reasonably good clinical improvements. On the other hand, many members of the medical community still believe that this treatment is in its initial stages and is not completely established.

To proceed with our recommendations and views about stem cell therapy, it is first imperative to understand the different types and sources of stem cells.

Broadly speaking, stem cells are of two types:

Autologous stem cells are those which are obtained from the patient’s own body.

They may be obtained from

Bone Marrow

Abdominal Fat

Umbilical Cord

Allogenic stem cells are those procured from matched related or unrelated donors. These may be subdivided into those of embryonic origin or non-embryonic origin such as the cells procured from another person’s umbilical cord.

Based on the way these cells are processed, there are two sub-classifications:

I. Minimally manipulated: Minimally manipulated stem cells are those which are transplanted without altering their fundamental nature.

II. More than minimally manipulated: More than minimally manipulated stem cells are those which are transplanted after significantly altering their fundamental nature.

The following is the view of Autism Connect and is meant to help parents decide:

Based on a review of the literature, along with the information available in the public domain and personal discussions with parents who have already taken stem cell therapy for their children, we believe that stem cell therapy definitely offers a potential medical solution to healing those parts of the dysfunctional brain that cause autism.

1. We are in agreement with the statement made in the white paper published by the International Society for Cellular Therapy with regard to two aspects

  • The right to seek treatment:

    "Patients seeking medical treatment for cellular therapies have the following rights that must be respected by healthcare providers and all associated with their care. a. The right to seek treatment: patients and their families/partners have the right to seek treatments for their diseases. No entity should withhold this fundamental right unless there is a high probability of harm to the patients. b. The right to information: patients have the right to an accurate representation regarding the safety and efficacy record of the cell treatment. This includes probable side-effects and a truthful record of efficacy. c. The right to informed consent: patients have a right to a true informed consent process that includes all the elements described above."

  • Distinction between legitimate medical stem cell therapy services and fraudulent services:

    "The following guidelines are useful in assessing scientific rigor and for differentiating between legitimate cell therapy medical services (including clinical trials and medical innovation) and fraudulent cell therapies."

    • Peer review and transparency: consumers of cell therapy medical innovation should evaluate evidence from peer-reviewed publications, professional society presentations and scientific recognition. They should be encouraged to seek multiple professional opinions and have all questions answered to their satisfaction.
    • Safety and regulatory history: patients should consider the reputation of the investigator and clinic, as well as the record of disciplinary activities against these entities.
    • Informed consent:patients should expect to be informed fully and accurately of the risks, benefits, costs, safety, compensation for injury, investigator conflicts of interest and alternative therapies, as a minimum."

Bearing this in mind, as a minimum, below are our recommendations to parents looking at the option of stem cell therapy for their children

(Please note that this is not a substitute for a formal medical advice and all parents are required to do their own due diligence before making this important decision.)

All parents should initially try the conventional rehabilitative treatment such as occupational therapy, speech therapy, ABA, etc. They should also take all the medications advised by the pediatric neurologists/psychiatrists/other physicians to control symptoms such as epilepsy, hyperactivity, etc. Complementary treatment such as dietary regulation, supplements, etc. may also be considered. Stem cell therapy should be considered only for those where despite all conventional rehabilitation, the child continues to remain significantly symptomatic.

Once parents have decided to consider stem cell therapy, the next important decision would be which type of stem cells to take and where to undergo the therapy. The following is our view in this connection:

We believe in safety first and therefore recommend that at this stage of evolution of stem cell therapy, it is safer to use:

A. Autologous stem cells

B. Minimally manipulated stem cells

C. Bone marrow derived stem cells (since these are obtained by a needle aspiration only, as compared to abdominal fat stem cells, which require a surgical procedure of laparoscopy to extract the fat from the abdomen).

 

We would also recommend that parents should consider only those centres that have published their safety and clinical research in scientific medical journals.

The reason for this is that when something is published in a medical journal, it is considered as peer-reviewed. This means that someone apart from the treating doctor has reviewed the safety and efficacy of the treatment and considered it worthy and accurate enough to be published in their journal. We believe that information on hospital and clinic websites online is not good enough, since there is no system of checks and balances to ensure that only authentic and accurate information is put up on the website.

On review of the medical literature through the PubMed scientific database, we have found that the following centers have published their clinical results in medical journals. These are listed in the chronological order of date of publication:

1. NeuroGen Brain and Spine Institute, Mumbai, India

Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 12

Main Publication: Autologous bone marrow mononuclear cell therapy for autism - an open label proof of concept study. Stem cell international. 2013(2013), Article ID 623875, 13 pages. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Anjana Nagrajan, Amruta Paranjape, Pooja Kulkarni, Akshata Shetty, Priti Mishra, Mrudula Kali, Hema Biju, Prerna Badhe. Click here to access full text article.

The above publication, along with 11 more publications on autism from this institute, can be accessed here

2. Shenzhen Beike Biotechnology Co Ltd Shenzhen China

Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 1

Yong-Tao Lv, Yun Zhang, Min Liu, Jia-na- tiQiuwaxi, Paul Ashwood, Sungho Charles Cho et al. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal of Translational Medicine 2013, 11:196

The above can be accessed here

3. Emcell, Kyiv, Ukraine.

Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 1

Bradstreet JJ, Sych N, Antonucci N, Klunnik M, Ivankova O, Matyashchuk I, M Demchuk; Siniscalco D. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. 2014;23 Suppl1:S105-12

The above can be accessed here

4. Duke Centre for Autism and Brain Development, Duke University Medical Centre, Durham, USA

Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 1

Dawson, Geraldine, Jessica M. Sun, Katherine S. Davlantis, Michael Murias, Lauren Franz, Jesse Troy, Ryan Simmons, Maura Sabatos‐DeVito, Rebecca Durham, and Joanne Kurtzberg. "Autologous cord blood infusions are safe and feasible in young children with autism spectrum disorder: Results of a single‐center phase I open‐label trial."Stem Cells Translational Medicine 6, no. 5 (2017): 1332-1339.

The above can be accessed here

 

Although many centers all over the world claim to get good clinical results with stem cell therapy, there is no way we can authenticate or validate those claims. Hence, our recommendation to parents is to preferably consider the centers, whose work is published.

What is stem cell therapy?

Recently, stem cell therapy is evolving as a new treatment for various incurable disorders such as autism. This therapy aims at replacing the damaged cells of the body using healthy cells. In autism, selective areas of the brain are damaged and do not function normally. Hence, this therapy helps in repairing and restoring the affected functions and thereby improving the quality of life of the individuals affected with autism. It helps to make these children independent and integrate them into the society.

What are stem cells?

Stem cells are the fundamental elements forming all the tissues of the human body. They are unique cells with an ability to rapidly multiply and convert into any type of tissue in the body. The main purpose of these cells is to regenerate, repair and replace damaged tissue. They are naturally capable of travelling towards the damaged areas and start the repair process.

What are the different types of stem cells?

There are many types of stem cells, but broadly they are classified into 3 types:

Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of mammalian embryos in the blastocyst stage on the fifth and sixth day after fertilization. They are derived from embryos that have been fertilized in vitro (in laboratory) in an in vitro fertilization clinic. Embryonic stem cells are distinguished by two distinctive properties: their pluripotency i.e their ability to form any cells of the body and their ability to multiply indefinitely. Because of these properties, embryonic cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. These cells are grown in culture medium in the laboratory at a suitable temperature and humidity where they divide and multiply indefinitely.

Some of the advantages of embryonic stem cells are:

  1. Embryonic stem cells are able to form any cell type of the body, and are more versatile than other stem cells

  2. These cells are considered immortal as they can be maintained in undifferentiated state for a very long time in controlled conditions.

Some of the disadvantages of embryonic stem cells are as follows:

  1. These cells can sometimes divide uncontrollable, forming tumors and growths madeof unwanted tissues.

  2. Human embryos are destroyed in the process of collecting these cells.

  3. These cells are related with many immunological rejections that results from the expression of MHC proteins.

  4. It is very expensive.

Umbilical cord is a rich source of stem cells which are either obtained from umbilical cord blood or Wharton Jelly. There are a variety of stem cells which can be obtained from the Umbilical cord namely hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and unrestricted somatic stem cells (USSCs) and other non- hematopoietic stem cells. Use of these cells has been currently approved for treatment of leukemias, lymphomas, anemias and inherited metabolic disorders. Numerous clinical trials are being conducted to study their potential in disorders like cerebral palsy, autism, ALS, etc.

The umbilical cord is collected and stored in a cord blood bank which is either public or private bank.

The advantages of using umbilical cord derived stem cells are:

  1. It is a non-invasive source and can be obtained from the umbilical cord immediately after birth.

  2. Available in vast abundance; thousands of babies are born each day and the umbilical cord and placenta are discarded as waste.

  3. Despite its high content of immune cells, it does not produce strong graft-versus- host disease

  4. Therefore, cord blood grafts do not need to be as rigorously matched to a recipient as bone marrow grafts.

Along with these advantages there are also few disadvantages of using umbilical cord stem cells such as:

  1. Engraftment of transplanted cells is slow as compared to other cell sources

  2. The volume of cells obtained from one umbilical cord is limited and low. Also, additional cell dose cannot be obtained.

  3. Few occurrences of infection have been recorded on use of these cells.

  4. There may be storage related issues such as loss of viability due to long term storage, Cost related to long term storage, etc

  5. Quality control

Stem cells are found in our body during all stages of life, number of stem cells and their ability to differentiate into different cell types differs as per the age of the person. Different types of stem cells are available in the body. There are stem cells that are tissue specific and are committed to differentiate only in one type of tissues. But adult stem cells can also be multipotent, with ability to be able to differentiate into different cell types.

Niches are the specific areas from where these cells can be procured. Adult stem cell niches have been found in most organs of the human body, eg. liver, brain, bone marrow, fat tissue, heart, nasal ensheathing cells, tooth pulp tissue etc. Whenever there is an injury or wear tear in the body these cells initiate the repair process. These are not only the cells from that particular tissue but the stem cells from bone marrow are mobilized to the peripheral blood and to different organs. This repair process is their primary role. Adult stem cells are a non-controversial and safe option for use in human subjects as they can be used autologously.

To date, published scientific literature indicates that adult stem cells have been derived from brain, bone marrow, peripheral blood, dental pulp, spinal cord, blood vessels, skeletal muscle, epithelia of the skin and digestive system, cornea, retina, liver, and pancreas; thus, adult stem cells have been found in tissues that develop from all three embryonic germ layers. However they cannot be procured easily from all of these sources; most common sources are bone marrow, abdominal fat and dental pulp.

Most of the beneficial effects of adult stem cells are also because of the paracrine effects of these cells on surrounding tissues. Paracrine effects are the changes induced in the functioning of cells surrounding these stem cells in the body. These are mediated through different chemicals secreted by the tissue. These paracrine effects are reduction in inflammation, neo-angiogenesis, immunomodulation and stimulation of local resident stem cells.

Bone Marrow Derived Cells

Different types of stem cells have been found to be present in the bone marrow, which differ in their potential to differentiate and form cells from one or more germ layers.

Initially, the bone marrow was thought to contain only hematopoietic stem cells. However, increasingly, evidence is pouring in regarding the heterogenous population of cells having varying plasticity. Mononuclear cells obtained from the bone marrow are a mixture of heamatopoietic stem cells, mesenchymal stem cells, very small embryonic like stem cells etc. Therefore these is a mixture of different types of stem cells in this tissue fraction.

Adipose tissue derived cells:

The adipose tissue (AT) is a highly complex tissue. It consists of mature adipocytes, preadipocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, resident monocytes/macrophages and lymphocytes. Adipose tissue provides a rich source of pluripotent stromal cells.

Adult stem cells have no ethical issues as associated with embryonic- and fetal-derived cells and are less susceptible to malignant changes and genetic abnormalities.

How do stem cells work in autism?

Stem cells repair, regenerate and replace the damaged cells in the brain of the individual with autism.

Below are the mechanisms with which stem cells repair this damage:

1. They release growth factors which help to regulate the immune system of individuals with autism and have a healing and regenerative effect on damaged tissue.

2. They increase the blood supply to the damaged tissue by forming new blood vessels by a process called angiogenesis thereby helping in their repair process.

3. They can convert into any tissue type into which they are injected, thereby replacing non-functioning tissue.

4. They can multiply to form new cells

What are the results and improvements after stem cell therapy in autism?

The outcome of stem cell therapy in autism is remarkably positive. A decrease in aggressive behavior & hyperactivity, improved eye contact & attention span, improvements in communication & social skills are observed. Improvements are also reported in the PET-CT scan of the brain as the change in metabolic activity of the brain. These changes correlate to the clinical improvements confirming the positive effect of stem cell therapy in autism. Below is the summary of the results of the papers published.

Title of the paper Author Country Type of cells used Source Demonstrated Safety Efficacy
(Percentage of patients that improved)
Autologous bone marrow mononuclear cell therapy for autism - an open label proof of concept study. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Anjana Nagrajan,Amruta Paranjape, Pooja Kulkarni, Akshata Shetty, Priti Mishra, Mrudula Kali, Hema Biju, Prerna Badhe. India Autologus Bone Marrow Yes 91%
Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism Yong-Tao Lv, Yun Zhang, Min Liu, Jia-na-tiQiuwaxi, Paul Ashwood, Sungho Charles Cho, YingHuan,Ru-Cun Ge, Xing-Wang Chen, Zhao-Jing Wang, Byung-Jo Kim and Xiang Hu China Allogenic Umbilical cord Yes 49%
Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. Bradstreet JJ, Sych N, Antonucci N, KlunnikM ,Ivankova O, Matyashchuk I, M Demchuk; Siniscalco D. Ukraine Allogenic Aborted Fetuses Yes 78%
Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial Geraldine Dawson,Jessica M. Sun,Katherine S. Davlantis,Michael Murias, Lauren Franz,Jesse Troy,Ryan Simmons, Maura Sabatos-DeVito,Rebecca Durham, Joanne Kurtzberg USA Autologous Umbilical cord Yes 52%