Movement Disorders Clinical Research

Clemens Scherzer - Laboratory of Neurogenomics

To decipher the three dimensions of the transcriptional code of Parkinson’s - modulation of transcript abundance, splice structure, and RNA editing - and the mechanisms by which transcriptional information is compromised and perturbs biological systems and phenotypes.

While the number of human genes has shrunken to an estimated ~22,000, the recent discovery of a hidden universe of an ever-increasing number of >100,000 unique transcripts is revolutionizing our thinking about gene-RNA interactions in human disease.

In complex neurodegenerative diseases such as Parkinson’s, susceptibility variants and epigenetic risks (from aging and environmental exposures) exert their disease-causing effects through modulation of transcript abundance, splice structure, and editing of transcript sequence. Dr. Scherzer's laboratory uses transcriptomics, computation, and systems biology to solve this fundamental question and strives to rapidly translate insights into a personalized neurology.

This pioneering way of looking at Parkinson’s and neurologic disease has allowed deciphering critical bits of transcriptional code on onset mechanism, novel therapeutic targets, and causal transcripts.

The Parkinson's Transcription Project

Newly launched, the Parkinson’s Transcriptome Project uses massively parallel, deep sequencing of 100 Parkinson’s and 100 control dopamine neuron transcriptomes to fully realize our vision of capturing and breaking the complete transcriptional code of Parkinson’s.

Clinical Implementation

Beyond discovery, we strive to translate our transcriptional targets into new therapies (using high-throughput drug screens) and our transcriptional markers into novel diagnostics.

Vikram Khurana - Khurana Lab

Khurana Lab

Stem cell approaches promise to transform the understanding and treatment of neurodegeneration

At Brigham and Women’s Hospital, Vikram (Vik) Khurana leads an effort that uses cutting-edge stem-cell technologies to make nerve cells (“neurons”) and mini brain “organoids” from blood or skin cells from patients with neurodegenerative diseases like Parkinson’s disease. Khurana and colleagues were among the first to identify abnormalities in stem cell-derived neuron models from Parkinson’s disease patients, and to reverse these abnormalities with drug-like molecules (Chung*, Khurana* et al. Science 2013).

Stem cell approaches for multiple system atrophy, Parkinson’s disease and related disorders

Stem-cell efforts are now being extended to other neurodegenerative diseases, with an initial focus on multiple system atrophy (MSA) and the cerebellar ataxias. MSA involves the misfolding of the same protein that has been implicated in Parkinson’s disease so we have every reason to believe that our Parkinson’s findings might help MSA patients. We aim to create a national stem cell bank for patients with these diseases.

Biomarkers and clinical trials

Based on our previous bench research, we are actively planning clinical studies to advance biomarker and treatment development. We have a major interest in repurposing FDA-approved drugs for neurodegenerative diseases. We are currently testing some interesting candidates in cellular and animal synucleinopathy models. We also regularly enroll our patients in clinical research opportunities available to them at Harvard Medical School and the broader Boston biomedical community.

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