Harvard College

Children's Medical Center Corporation

The General Hospital Corporation

Brian J Wainger

Clifford J Woolf

Kevin Eggan, Jr

Evangelos Kiskinis

Kevin C Eggan

Justin K Ichida

Esther Yesde Son

Kevin Carl Eggan

The specification provides compositions and methods to treat neurodegenerative diseases.

Methods to treat neurodegenerative diseases

The present invention provides methods of transdifferentiation of somatic cells, for example, directly converting a somatic cell of a first cell type, e.g., a fibroblast into a somatic cell of a second cell type, are described herein. In particular, the present invention generally relates to methods for converting a somatic cell, e.g., a fibroblast into a motor neuron, e.g., an induced motor neuron (iMN) with characteristics of a typical motor neuron. The present invention also relates to an isolated population comprising induced motor neurons (iMNs), compositions and their use in the treatment of motor neuron diseases such as ALS and SMA. In particular, the present invention relates to direct conversion of a somatic cell to an induced motor neuron (iMN) having motor neuron characteristics by increasing the protein expression of at least three motor-neuron inducing (MN-inducing) factors selected from Lhx3, Ascl1, Brn2, Myt1l, Isl1, Hb9, Ngn2 or NeuroD1 in a somatic cell, e.g., a fibroblast to convert the fibroblast to an induced motor neuron (iMN) which exhibits at least two characteristics of an endogenous motor neuron.

Conversion of somatic cells into functional spinal motor neurons, and methods and uses thereof

The present invention is based on the discovery that motor neurons derived from patients with a neurodegenerative disease have decreased delayed rectifier potassium current and increased persistent sodium current compared to motor neurons derived from control healthy individuals. The present invention is also based on the discovery that the class of compounds known as 'potassium channel openers' can be used to treat neurodegenerative diseases, including ALS, Parkinson's disease, Alzheimer's disease, epilepsy, and pain.

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Brookline, MA, United States of America

Brian J Wainger