Autism answers within genetic disorders

Collaboration aims at drug discovery pipeline for monogenic causes of autism

February 24, 2021
Ilene Schneider
Autism answers within genetic disorders

NEW YORK—A collaboration between Rumi Scientific and the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai is aiming to develop a drug discovery pipeline for rare genetic disorders that carry a high risk of autism. 

At the outset, the project will create and use a platform that imitates the development of brain tissues, at high speed. The research will enable researchers to learn how cells respond to three known genes associated with autism.

As Dr. Joseph D. Buxbaum, director of the Seaver Autism Center and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine, explained, “Over the past several years, more than 100 genes that confer very high risk to autism when mutated have been identified.” He added that the Seaver Autism Center is “eager to work together with Rumi Scientific,” using its “outstanding proprietary technology to build a drug discovery pipeline for these monogenic causes of autism, with the ultimate goal of identifying lead therapeutic candidates that can be evaluated clinically.”

Rumi Scientific of New York attempts “to revolutionize drug discovery, using synthetic human tissue to produce more predictive data leading to a safe and faster clinical trial process,” according to its website.  Founded in 2016 on technology initially conceived at Rockefeller University, Rumi Scientific uses a phenotypic platform to mimic the development of human brain tissues, at high speed. Its proprietary technique creates highly reproducible organoids. These tiny, self-organized tissue cultures that are derived from induced pluripotent stem cells (iPSCs) can be crafted to replicate an organ or to express selected aspects such as genetic mutations. 

Rumi’s system incorporates sensitive machine-learning algorithms. By helping to very precisely identify effects on a cell, the system can predict the therapeutic effect a drug could have on a human’s diseased brain tissues. This advanced technology enables researchers to identify and quantify differences between diseased and healthy cells. Rumi’s organoids focus on early development phenotypic signatures to determine the way in which a gene mutation leads to disease. Because a large portion of autism genes are active even early in development, these tissue cultures may present interesting possibilities for drug screening. 

Mount Sinai’s Seaver Center will provide patient-derived and engineered stem cells to Rumi, which will create tissue cultures to express specific genetic mutations. These cultures offer understanding into how gene mutation leads to autism and the potential for finding drugs to treat it. Mount Sinai will start by providing iPSCs for three autism genes: ADNP, DDX3X, and FOXP1. Rumi Scientific will probe the existence of phenotypic signatures associated with these genetic mutations using its proprietary organoid technology. The objective of creating a model platform for each of the three genes of interest is to enable translation of these proof-of-concept experiments into a robust, high-throughput screening platform across which thousands of therapeutic compounds can be efficiently tested. 

Buxbaum added, “The collaboration is to produce human neural cell organoids in lab dishes and see if we can develop a platform for mid-throughput drug screening. ADNP was one of three genes selected. We have focused on three genes that are involved in development, since the assay reflects early brain development.”

According to Sandra Bedrosian-Sermone, president of the ADNP Kids Research Foundation, “ADNP is repeatedly identified as one of the top genes for autism and developmental delay. We can’t be more thankful to both Mount Sinai and Rumi Scientific for selecting ADNP in this potentially life-changing study that could help find treatments for individuals with ADNP syndrome.”

“To date, no one has evaluated how specific autism mutations affect neural organization in a human context and at the level of a tissue; this collaboration creates the opportunity to discover robust phenotypic signatures which in turn could lead to valuable therapeutic possibilities,” said Ilona Nemeth, CEO of Rumi Scientific. She said that the first portion of the partnership, growing out the cultures, should be finished by the middle of the year.

"It's time to start thinking about using precision medicine in developmental disorders like autism," concluded Buxbaum, who hopes that assays for drug discovery could be ready next year.

The two organizations started talking about the partnership in early 2020. Mount Sinai is Rumi's first academic institution partnership.

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