Stories about: Robin Kleiman

Muscular dystrophy study suggests new therapeutic approaches to autism

muscular dystrophy autism social interaction
In addition to weakening muscle cells, loss of dystrophin also impairs Purkinje cells in the cerebellum.

Robin Kleiman, PhD, is Director of Preclinical Research at Boston Children’s Hospital’s Translational Neuroscience Center.

One of the hardest parts of developing new treatments for autism spectrum disorder (ASD) is that almost every patient has a different combination of environmental and genetic risk factors. This suggests that every patient could take a unique path to their diagnosis. It is hard to come up with a single treatment that will help patients with fundamentally different root causes of ASD.

One way to approach this problem is to look for ways to cluster sub-types of autism for clinical trials, based on genetic risk factors or the types of neural circuits that are affected. If circuit dysfunction could be monitored and diagnosed easily in patients, it might be possible to develop treatments to reverse the dysfunction that cut across genetic and environmental causes of ASD. That is the hope of research on well-defined “syndromic” causes of autism such as tuberous sclerosis complex, Fragile X syndrome and Rett syndrome.

Accelerating research collaborations to design clinical trials for children with brain disorders, including ASD, is a major mission of Boston Children’s Hospital’s Translational Neuroscience Center (TNC). A recent study in Translational Psychiatry, led by Mathew Alexander, PhD, in the Boston Children’s lab of Lou Kunkel, PhD, in collaboration with the TNC and Pfizer, is a prime example. It suggests that patients with Duchenne muscular dystrophy (DMD) may constitute another subset of ASD patients — one that could benefit from phosphodiesterase (PDE) inhibitors, a family of drugs including Viagra.

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The genetics of early-onset psychosis: Could it aid understanding of schizophrenia?

psychosis schizophrenia
(Thomas Zapata/Wikimedia Commons)

At age six, Matthew (not his real name) began hearing voices coming out of the walls and the school intercom, telling him to hurt himself and others. He saw ghosts, aliens in trees and color footprints. Joseph Gonzalez-Heydrich, MD, a psychiatrist at Boston Children’s Hospital, put Matthew, at age 9, on antipsychotic medications, and the hallucinations stopped.

It’s rare for children so young to have psychotic symptoms. Intrigued, Gonzalez-Heydrich referred Matthew for genetic testing.

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When preclinical studies get dosing wrong, new drugs get lost in translation

Robin Kleiman, PhD, is Director of Preclinical Research at Boston Children’s Hospital’s Translational Neuroscience Center.

drug dosing preclinical studies

Basic research investigators are increasingly conducting translational research studies to advance their therapeutic approaches to clinical trials. Unfortunately, when testing drugs in rodent models of human disease, these studies often do not measure drug levels from their animal subjects to determine drug dosing.

This is understandable, since collecting these data can be very expensive and requires specialized expertise. But as a consequence, a lot of preclinical literature is published without any consideration of what drug concentration was actually achieved in the organ of interest. This is undercutting our efforts to get new therapies to patients.

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