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Can Topotecan Relieve Angelman Syndrome?

Posted by Eileen Braun, executive director of the Angelman Syndrome Foundation, and Joe Horrigan, M.D., Autism Speaks assistant vice president and head of medical research.
Today brings the publication of findings on a group of compounds whose potential for treating Angelman syndrome deserves both kudos and cautious optimism. This rare condition, often classified as an autism spectrum disorder (ASD), is marked by developmental delays, lack of language, seizures and difficulties with balance and walking. Many individuals with Angelman syndrome require lifelong care.
In research initially funded by the Angelman Syndrome Foundation, neurobiologist Ben Philpot and his team at the University of North Carolina, Chapel Hill, screened over 2,300 compounds to find several that, in mice, activate production of a brain protein whose absence causes Angelman syndrome in humans. The tremendous public interest in this report stems from the fact that one of the compounds identified in the paper is available as an FDA-approved chemotherapy drug (topotecan, or Hycamtin) for small cell lung cancer that fails to respond adequately to first-line treatments. [See our related news report, “Topoisomerase Inhibitors and Angelman Syndrome.”]
While we are heartened by the UNC team’s identification of potential medicines for the treatment of Angelman syndrome, we are deeply concerned that this news could produce  expectations that lead some families to prematurely seek this drug for their loved ones–that is, before it is safe to do so. As a community, we should welcome the news, but we cannot let it risk unintended harm by side stepping the proper due course of research. The next phase of research is critical to assessing safety and effectiveness.
Our concerns are several-fold: First, the findings from this study represent a very early stage of the drug discovery process. As the UNC scientists are quick to point out, they have yet to determine whether these compounds actually relieve symptoms in animal models of Angelman syndrome—let alone whether they can benefit children or adults affected by this disorder. Along the same lines, it is unclear if medicines like topotecan affect human cells in the same way that they affect the cells of mice. In addition, these agents can have serious side effects. For example, we must remember that chemotherapy drugs such as topotecan are designed to kill cells—primarily cancerous ones, of course. But they also affect healthy cells. Potential side effects of topotecan include bone marrow suppression, which is associated with a sometimes dramatic decrease in the production of blood cells. In addition, topotecan can cause fetal harm when administered to a pregnant woman.
On a practical level, determining an effective but safe dose of a medicine like topotecan can be difficult for even a cancer specialist. Also, a medicine like topotecan was not designed for use over extended periods of time, but rather as one of the last resorts for patients with a deadly form of cancer that does not respond adequately to other treatments. All of these factors need to be considered carefully by the readers of this important paper by Dr. Philpot and his colleagues.
We feel it is especially important to view this study’s promising findings in the light of other experimental medicines now entering the autism research pipeline. We look forward to these potential medical treatments being carefully studied for safety and effectiveness first in animal models and human tissue samples. Only then should the safest and best candidates be considered for advancement into clinical trials.
The critical point is that there are no short cuts to drug development when it comes to safety.
This raises a second, very important issue for our families. As promising as any experimental medicine may be, one needs to carefully consider what it means for you or your child to be part of a clinical drug trial. The potential benefits and risks associated with being a research participant can be quite different from those experienced as a person receiving medical care from a personal physician or other healthcare professional. As a result, the decision to become a research participant should be approached with careful thought and discussion.
For these reasons, we’re working together to create a “Participant’s Guide to Autism Drug Research.” Please look for its release on this science blog and on the “Participate in Research” page of Autism Speaks website in the coming weeks. You can also stay up-to-date with this research as it relates to Angelman syndrome via the Angelman Syndrome Foundation’s website at
Have more questions? Send them to and bring them to “The Doctors Are In,” our monthly live webchat with clinical psychologist and Autism Speaks Chief Science Officer Geri Dawson, PhD, and her co-host, pediatric psychiatrist and Autism Speaks Head of Medical Research Joe Horrigan, MD.