Therapeutic Opportuitues: ALS & Neuro-degenerative Diseases

Description:

Introduction

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease in the US, is the most common neurodegenerative disorder of young and middle aged adults that is incurable and invariably fatal. The only disease-modifying therapy currently available is Riluzole®, which only extends survival by 3-6 months and has recently come off patent. This treatment is expected to show sales in excess of US $129 million for 2007. Novel disease-specific mutations in a particular gene have recently been identified in ALS patients. This gene has not previously been associated with ALS, thereby opening up a whole new avenue of possible treatments to slow down or even reverse the process of cell degeneration in this condition and potentially other neurodegenerative disorders.

Technology

ALS is a fatal disease with an incidence of approximately two per 10,000. There is no effective cure for this condition. Our novel technology is a therapy of pre-formulation sterile, recombinant preparations of human angiogenin protein that can be delivered systemically to treat patients with ALS. This technology is a therapeutic treatment paradigm that could potentially delay disease progression and increase survival in ALS patients.

The angiogenin is based on the identification of loss-of-function mutations of the angiogenin gene in ALS patients. Our proof-of-concept research demonstrates the neuroprotective and disease-delaying effect of systemic angiogenin protein delivery in a mouse model of ALS (Figure).

- Angiogenin is enriched in motoneurons and a potent protective factor against neuronal cell death

- Angiogenin protein delivery significantly increased life-span and improved motor function in an established mouse model of ALS

- Angiogenin can be administered systemically with effect in mouse models of ALS

Applications

Dr Matt Greenway (currently at McMaster University, Canada) and Dr Orla Hardiman (currently at Trinity College Dublin) have studied ALS-specific mutations in angiogenin. Nature Genetics February 2006.

Prof Jochen Prehn, of the RCSI, and his collaborators have carried out key studies building on these findings showing that angiogenin is expressed preferentially in the spinal cord and is neuroprotective to motorneurons, both in cultures and in a mouse model of ALS (Greenway et al., Nat Genetics, 2006; Kieran et al., J Neurosci, 2008.). Angiogenin delivery has led to a functional improvement and increased life span when applied after disease onset in this mouse model. Currently both protein delivery-based and viral delivery-based therapeutic approaches are being developed by the team.

Advantages

This opportunity points to the development of new therapeutic products for ALS, an incurable and invariably fatal disease where only one disease-modifying therapy currently exists. Given that ALS is a relatively rare disease there is the potential that new agents will be awarded “orphan drug” status.

- The new approach is based on breakthrough work on a gene not previously associated with ALS

- There is the potential that disease-modifying drugs in ALS may have therapeutic effects in other more common neurodegenerative diseases

A patent has been issued under the title “Treatment of ALS and variants thereof consisting of primary lateral sclerosis (PLS) or spinal muscular atrophy (SMA)” (US patent number 7,659,243), relating to the use of angiogenin in the treatment and prevention of ALS and other neurodegenerative diseases. Additional intellectual property applications are currently under prosecution.

Contacts:

Dr. Gearóid Tuohy, RCSI Technology Transfer, 123 St Stephen’s Green, Dublin 2, Ireland.

Email: gearoidtuohy@rcsi.ie Tel: +353 1 4022362

Dr Aoife Gallagher, RCSI Technology Transfer, 123 St Stephen’s Green, Dublin 2, Ireland.

Email: aoifegallagher1@rcsi.ie. Tel: +353 1 4022394

Dr Liz Moran, Enterprise Ireland, East Point Business Park, Dublin 3.

Email: liz.moran@enterprise-ireland.com. Tel: +353 1 7272696

Principal Investigator:

Prof. Jochen Prehn, Dept. of Physiology & Medical Physics, Royal College of Surgeons, 123 St Stephen’s Green, Dublin 2, Ireland. Email: JPrehn@rcsi.ie Tel: +353 1 4022255

Direct Link:

http://rcsi.testtechnologypublisher.com/technology/4724

Category(s):

Regenerative Medicine

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For Information, Contact:

Gearoid Tuohy

Royal College of Surgeons Ireland

gearoidtuohy@rcsi.ie

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