Senesco Technologies Advances Genetic Cancer Treatment

by Jade Morgan
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Submitted by Jade Morgan as part of our contributors program.

Cancer plagues the human race like no other disease, killing roughly 1,500 Americans each day and 7.6 million people worldwide each year. Companies around the world aggressively conduct research to find cures for this pervasive disease. Among them is Senesco Technologies (SNTI), a biotech company steadily advancing its multiple myeloma cancer candidate through FDA clinical trials.

Senesco’s research in private laboratories and universities started over two decades ago, and the company was officially founded in 1998. The company is focused on a novel approach to cancer therapy based on its discovery of eukaryotic translation initiation Factor 5A (elF5A), a protein that functions as a genetic switch to modulate cell growth and cell death signals, which cancer cells exploit to support abnormal growth and the over-duplication that causes tumors.

Senesco originally worked with Factor 5A as a method to extend shelf life of food and increase crop yields, but it quickly discovered that the inverse activation of Factor 5A had profound implications for the treatment of cancer in all eukaryotic cells- including human cells.

Transitioning its legacy focus from bioagriculture towards human health, Senesco has attracted leading researchers and executives, including several men who have built and sold their own companies prior to joining Senesco. Although Senesco faces challenges in its journey to advance its Factor 5A technology through clinical trials, the company has thus far demonstrated progressive success with its technology in plant, rodent, primate and human patients.

Discovery: Factor 5A

When a cell has reached the end of its allotted life cycle, programmed cell death is naturally activated to ensure the overall health of the organism. This process is nature’s way of eliminating cells that are no longer required, including old, redundant or defective cells. In humans, this programmed cell death is referred to as apoptosis.

Some cells die prematurely, throwing off the balance of this natural cycle. This uncontrolled cell death leads to lysis of cells, which often results in disease or death of the organism. In plants, several variables such as weather and disease can accelerate cell death (a.k.a. senescence).

At the opposite end of this spectrum are cells that multiply, avoiding the process of apoptosis altogether- a trait of cancerous cells.

Because Factor 5A regulates both apoptosis and cell survival, it plays a critical role in determining whether a cell multiplies or enters the programmed cell death cycle. This characteristic often is the determination between human life and death.

Senesco has secured roughly 90 patents around the Factor 5A platform and has licensed agricultural applications of Factor 5A to develop productivity in a range of plant species, including fruits, flowers and vegetables. The company’s primary focus, however, is on its application of the gene to human healthcare.

Development: SNS01-T

In order to modulate apoptosis, Senesco has developed a gene regulation therapeutic candidate, SNS01-T, which was granted orphan drug status by the U.S. Food and Drug Administration. SNS01-T regulates Factor 5A by selectively triggering apoptosis in B-cell cancers to eliminate the cancer form of Factor 5A (hypusine) while over-producing a death-promoting form of the Factor 5A protein (lysine).

Application: Cancer

Cancerous cells begin as healthy cells that turn malignant as they accumulate multiple mutations in their genome. This accumulation enables the cell to grow uncontrollably, sidestepping the body’s natural process of apoptosis. As these cells continue to grow, they recruit nearby tissue to provide a blood supply for nutrition and inflammatory cells that can further promote tumor growth and development.

Senesco’s Factor 5A platform technology is concentrated on curbing both cell growth and cell death signals. Cancer cells are capable of exploiting cell death signals to further their abnormal growth and longevity, avoiding apoptosis. Senesco’s technology aims to reprogram these malignant cells and force them into programmed cell death by leveraging two major pathways triggered by the body’s immune system. The company has successfully demonstrated this by controlling Factor 5A. Apoptosis through both of these pathways can be triggered in several human cancer cell lines.

Application: Agriculture

In agricultural application of its technology, Senesco has formed licensing deals with major companies like Bayer, Scotts and Monsanto.

Because Factor 5A plays such a critical role in the process of cell death, Senesco has found that modulating the expression of the genes can lengthen the shelf life of perishable produce, increase seed yield, and enlarge plant size. The company’s technology has also demonstrated its ability to reduce complications stemming from environmental stresses and disease, which benefits consumers, farmers and agricultural companies.

Environmental stresses such as frost, drought, heat, and soil salinity pose a significant cost to global commercial agriculture. Senesco believes that its technology can have a positive impact by providing resistance against premature cell senescence.

The company’s technology has demonstrated efficacy in extending shelf life in bananas and tomatoes and has shown a direct impact of reducing natural senescence for significantly longer shelf life. Produce growers, marketers and consumers will benefit from this achievement by expanding the timeframe during which food is consumable and reducing waste due to rot. Because Senesco’s technology is implemented at the seed level, the use of chemical applications does not affect the taste, texture and other consumer traits of plant life.

Studies have also demonstrated Factor 5A’s ability to significantly increase the quantity of seed produced by plants. By ensuring that the plant continues to grow even through stressful periods, Senesco was able to maximize the output of plants by approximately 66% to 100% in test subjects. For farmers and agricultural companies, maximized seed output results in more yield and profitability.

Testing: Clinical Trials

A demonstration of Senesco’s Factor 5A cancer cell technology can be found in the results of the company’s Phase 1b/2a study of SNS01-T. Normally Phase 1 studies human toxicity study while Phase 2 then studies efficacy, but because Senesco was granted orphan drug status by the FDA, the company was given the go-ahead to proceed with a mixed Phase 1-2 study and administer its treatment for efficacy starting with the initial trial. Although there are many forms of cancer, Senesco focuses on multiple myeloma, a sheet-like cancer found in bone marrow. The company has already achieved positive results in this study.

As of August 2012, Senesco had completed the first cohort of its Phase 1b/2a clinical trial of SNS01-T in patients with advanced forms of multiple myeloma. In previous trials, these patients had no reaction or negative results from FDA approved-drugs like REVLIMID® and VELCADE®. In this cohort, Senesco reported that two out of three patients achieved stable disease, while one remained stable four weeks beyond the end of the dosing period. Results show the therapy was well-tolerated.

Senesco is now focusing on its second cohort. Enrollment is open, but the first patient has completed a dosing period. Patients in the second cohort either have multiple myeloma, diffuse large B-cell or diffuse mantle cell lymphoma. Senesco is recruiting patients at the Mayo Clinic in Rochester, MN, the University of Arkansas, and the Mary Babb Randolph Cancer Center in Morgantown, WV.

While these discoveries and achievements demonstrate applications to both plants and animals, the company maintains a primary focus on applying its technology to cancer treatment.

The Future: Advance Toward a Cure

For agricultural application, Senesco’s licensees of Factor 5A technology are currently advancing several programs to develop crops with enhanced growth and resistance to environmental stress and disease. The company’s most advanced program is that of licensee Rahan Meristem Ltd., where Chief Scientific Officer Eli Kayat presented on “Enhanced fungal resistance in transgenic banana plants (Musa acuminate AAA) expressing cottonwood (Populus sargentii) pathogen related eIF5A gene” at Tel Aviv University in February 2012.

For cancer treatment, Senesco continues to advance SNS01-T through clinical trial and development. For 2013, the company expects to complete its Phase 1b/2a multiple myeloma trial with SNS01-T. By year-end, Senesco anticipates the initiation of a Phase 2b study of the therapeutic candidate and has begun to consider partnerships to support clinical trials of Factor 5A.

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