Stem Cell Therapy For Autism

Antonio L. Dans, MD
Professor UP College of Medicine Department of Clinical Epidemiology and Department of Internal Medicine President Philippine Society of General Internal Medicine (PSGIM) Academician National Academy of Science and Technology

Declaration of Conflicts of Interest

Not an expert in stem cell therapy Not an expert in autism No stocks in stem cell products No payments for this lecture

Outline
What is Stem Cell Therapy Why Trials Are Required? (2) Is Autism an Exception? (3) How Do We Go Forward? (3)

http://pubs.rsc.org

Outline
What is Stem Cell Therapy Why Trials Are Required? (2) Is Autism an Exception? (3) How Do We Go Forward? (3)

CASE REPORT 70 year old diabetic male. Right calf pain on exertion since 3 years. Past 2 weeks, noted worsening leg pain and dark discoloration of the right foot. Diagnosis was critical limb ischemia (patient in danger of amputation). Given autologous stem cell therapy (bone marrow derived mononuclear cells). Over next 3 months, symptoms improved. Limb was successfully salvaged no amputation was done. Does this treatment seem effective?

16/19 SAVED BY STEM CELL THERAPY

CASE REPORT CASE SERIES

20/21 SAVED BY PLACEBO

CLINICAL TRIAL

Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized-start, placebo-controlled pilot trial. - Walter DH et al. Circulation Cardiovascular Interventions 2011

Why We Need Trials: #1: To Assess Effectiveness

Reasons Why Patients Get Better After Treatment Maybe it was a placebo effect. Maybe the patient received other treatments. Maybe the body healed itself.

GOD HEALS
WE CHARGE

#2 To Assess Side Effects

1. formation of ectopic tissue including development of new malignant tumors, 2. aggravation of existing cancers (enhanced tumor spread, metastasis, and anti-cancer drug resistance), 3. severe allergic reactions, 4. obliterative bronchiolitis, 5. graft versus host disease (rash, nausea, vomiting, abdominal pain, intestinal bleeding, jaundice, pericarditis, pleural effusion), 6. infections (pneumonia, meningitis, sepsis) and many other side effects.

Outline
What is Stem Cell Therapy Why Trials Are Required? (2) Is Autism an Exception? (3) How Do We Go Forward? (3)

Exception #1: Miraculous treatment

Definition of a Miracle Treatment

Course of disease is uniformly poor New treatment greatly improves the usual course There is no other explanation for the improvement.

Exception #2: Innovative Therapy

Novel medical interventions, radically different from the standard of care, provided in order to benefit a patient, rather than to acquire new knowledge. Innovative therapies are often devised by clinicians, not basic science researchers; It may be difficult to reduce a patient to a randomized research subject

Opinion by Taylor P Journal of Law, Medicine and Ethics 2010

Innovative Therapy

Robert Gross did open heart surgery for PDA in 1938

Hemicorporectomy for pelvic malignancy 1960

Exception #2: Innovative Therapy

Novel medical interventions, radically different from the standard of care, provided in order to benefit a patient, rather than to acquire new knowledge. Innovative therapies are often devised by clinicians, not basic science researchers; It may be difficult to reduce a patient to a randomized research subject clinician-scientists commit to promptly use their experience with individual patients to contribute to generalizable knowledge, including moving to clinical trials after a few patients Opinion by Taylor P Journal of Law, Medicine and Ethics 2010

ISSCR Guidelines for the Clinical Translation of Stem Cells (2008)

Recommendation 34: Clinician-scientists may provide unproven stem cell-based interventions to at most a very small number of patients outside the context of a formal clinical trial, provided that: h. there is a commitment by clinician-scientists to use their experience with individual patients to contribute to generalizable knowledge. This includes: i. ascertaining outcomes in a systematic and objective manner; ii. a plan for communicating outcomes, including negative outcomes and adverse events, to the scientific community to enable critical review (for example, as abstracts to professional meetings or publications in peer-reviewed journals); and iii. moving to a formal clinical trial in a timely manner after experience with at most a few patients.

ISSCR Task Force on Unproven Stem Cell Treatments 2010

application of medical innovation in the stem cell field should be confined to a very limited number of cases, should be subjected to external review and stringent oversight, and should move quickly towards a formal research study. Indeed, this Task Force argued that medical innovation be limited to no more than two participants.

Exception #3: Compassionate Use

Protection vs. false hope?

OR

denial of her only hope?

Helsinki Declaration
35. In the treatment of a patient, where proven interventions do not exist or have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorized representative, may use an unproven intervention if in the physicians judgement it offers hope of saving life, re-establishing health or alleviating suffering. where possible, the innovative treatment should also be made the object of research, designed to evaluate its safety and efficacy.

Outline
What is Stem Cell Therapy Why Trials Are Required? (2) Is Autism an Exception? (3) How Do We Go Forward? (3)

#1: External Regulation

Philippine FDA Act of 2009

'Health products' means food, drugs, cosmetics, devices, biologicals, vaccines, in-vitro diagnostic reagents and household/urban hazardous substances and/or a combination of and/or a derivative thereof. It shall also refer to products that may have an effect on health which require regulations as determined by the FDA. Drug means: articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals.

#2: Proper Research

Status of Research
Studies on Stem Cell: 121, 428 Randomized Clinical Trials: 378 On Autism: 0 Ongoing Trials: 200+ On Autism: 2 Philippine Involvement: 0

#3: Publication

About Charges
The payment of services for certain unproven applications in stem cell therapies can be defined without necessarily measuring it only in pesos or dollars. Crucial in determining the cost of an innovative service is differentiating the cost of supplies from that of outright personal service. We cannot completely adopt Western practices of offering these investigational therapies completely free to clinical trial participants. This approach will not only be unaffordable for our institutions but very expensive and will forever relegate us to be a marketing testing ground after others have developed a technique in their country. - Sec. Ona, Aug. 12, 2013

CBCP Statement
Clinical research trials should not be misrepresented as therapeutic stem cell treatments. Clinical research trials are intended to gather scientific data for developing future stem cell therapies. These trials do not guarantee cures and carry greater risks to participants than approved therapeutic treatments. Participation in these trials is voluntary and must not require payment. To charge payment is a violation of research ethics and an exploitation of research subjects.

Stem Cell Therapy Where are the Publications?

Outline
What is Stem Cell Therapy Why Trials Are Required? (2) Is Autism an Exception? (3) How Do We Go Forward? (3)