Experimental Design: New Therapies Are Being Developed to Treat Lifelong Illness

Finding cures for lifelong illness is arguably the core motivating factor for clinical research professionals. Unfortunately, it’s seldom the reality. More realistically, researchers are hoping to develop a treatment that can improve the quality of the patient’s life by reducing the symptoms or slowing the progression of the disease. 

In this post, we explore some of the experimental treatments being developed to help patients manage their lifelong conditions.

Huntington’s Disease

Huntington’s is a neurodegenerative disease with the brain affected by aberrant proteins. Researchers are testing if a gene-silencing drug can slow the disease’s progression, explains science journalist Asher Mullard. The Phase III trial from Roche and Ionis’s RG6042, if successful, will bring benefits to patients not just with Huntington’s disease but other neurodegenerative diseases too.

Those with Huntington’s have a mutant huntingtin protein (mHTT), Mullard says, which can cause the onset of the disease, bringing motor, cognitive and psychiatric effects.The belief is that toxic mHTT fragments affect cellular pathways.

Mullard reports that current drugs to treat Huntington’s control chorea, but experimental gene-silencing therapies aim to disrupt the course of the disease. Questions remain whether they will be effective. For instance, researchers need to determine the best means of delivering gene-silencing drugs to tissues most in need. 

Another gene therapy to treat the mutant Huntington’s gene is AMT-130, which aims to bring about a permanent change in the patient’s genetics, writes Anna Pfalzer, clinical research fellow in the Department of Neurology at Vanderbilt University Medical Center. 

AMT130 can deliver to patients the harmless adeno-associated virus (AAV), which carries an extra bit of genetic code — added by researchers — to neurons. That extra bit of code sends instructions to the body to make a huntingtin-lowering drug.

“Once a neuron is treated with AMT-130, it will continuously manufacture additional copies of the new Huntingtin-lowering molecule. So while the neuron still contains the harmful HD gene, and still sends messages to make the mutant huntingtin protein, at the same time it will be producing a new set of instructions to delete the huntingtin message. The result should be reduced production of the harmful protein, with a very long duration of effect – possibly lifelong,” explains Pfalzer.

Parkinson’s Disease

A drug that helps to treat benign prostatic hyperplasia (enlarged prostate) might be a key therapy to slow down the progression of Parkinson’s. Existing Parkinson’s treatments aren’t able to slow down the rate of neuron loss, but Terazosin could activate the PGK1 enzyme, which would prevent brain cell death, reports Michelle Roberts, health editor at BBC News.

Using medical records as a resource, researchers from the University of Iowa and the Beijing Institute for Brain Disorders in China, identified 2,800 men with BPH and Parkinson’s that were on Terazosin or similar PGK1-targeting drugs and compared them with 15,409 Parkinson’s patients using a different treatment for BPH.

The results showed the Terazosin and similar drug group performed better on Parkinson’s disease symptoms and progression. Clinical trials are slated to begin soon.

Lifelong Illness

Type 1 Diabetes

Replacing missing cells with cell therapy is becoming an important tool in treating diabetes. Indeed, it could be one of the best chances the industry has for curing diabetes, says biotech journalist Clara Rodríguez Fernández

Patients would have their missing insulin-producing cells replaced, start producing insulin normally and rid themselves of the disease. So far, transplanted pancreatic cells have had a poor success rate because host bodies reject the implanted cells, explains Rodríguez Fernández.

But the Diabetes Research Institute in the U.S. is developing a bioengineered mini-organ that covers insulin-producing cells in a protective barrier. And it has been successful, with the first patient in Europe treated in 2016 no longer needing insulin therapy.

  • Viacyte and JDRF are also working on creating a protective barrier device, having proven the device safe during their Phase I trial. 
  • Orgenesis in Belgium is also working on new treatments by transforming liver cells into insulin-producing cells so donor cells are no longer required. 
  • Islexa, in the UK, is trying to develop a similar procedure by reprogramming pancreatic tissue.

Crohn’s Disease

Modifying the cells of patients with Crohn’s Disease has shown positive results using human cells. A clinical trial of the treatment  is set to begin soon, says the team at NIHR Guy’s and St Thomas’ Biomedical Research Centre (BRC). 

Researchers studied Crohn’s patients’ white blood cells and compared them with the cells of healthy people to develop the technique. They then grew patients’ cells in a special culture to make them behave similarly to healthy people’s cells.

Former director at BRC Graham Lord led the research and says that the cell modification technique is an advancement in cell therapies. It treats more than the symptoms; it aims to reset patients’ immune systems. 

Lifelong Illness

Chronic Obstructive Pulmonary Disease 

Back in 2005, a study population of 2,164 COPD patients and 500 patients without COPD participated in the first large observational study of the disease that was sponsored by pharma company GSK. It lasted three years, explains Ruth Tal-Singer, vice president of medical innovation at GSK’s research and development department. 

Using data from that study, researchers described a group of participants with Multi-Organ Loss of Tissue (MOLT), who experienced worsened emphysema and osteoporosis over the three-year period. Additionally more patients from this group died or needed to be hospitalized. The MOLT group shared a pattern of protein biomarkers which suggested their bodies were unable to repair tissue. 

Another group of patients from that original study had inflamed biomarkers in their blood. They all had a high incidence of cardiovascular disease, high blood pressure and diabetes. Cardiovascular disease is a major cause of COPD exacerbation.

The point, Tal-Singer says, is that COPD cannot be treated with a one-size-fits-all approach and requires a deep understanding of patients’ particular biomarkers. What is needed is further examination of the data to guide and improve new studies.

Pain Management for Sickle Cell Patients

Sickle cell patients that arrive at a hospital emergency department (ED) tend to be experiencing serious pain from an acute vaso-occlusive episode (VOE). The problem is that the ED approach to pain doses is not standardized, leading to mixed feedback from patients about how effective the analgesic was. This is why the Duke Clinical Research Institute and the Duke University School of Nursing joint study (COMPARE-VOE) is important.

“VOE pain can be sudden, excruciating, and unpredictable,” says Huiman Barnhart, principal investigator for the DCRI’s data coordinating center for COMPARE-VOE. The current non-standardized approach can mean patients’ pain is not adequately managed.

The researchers are using a patient-specific approach, which relies on an algorithm that accommodates dose variation according to patients’ needs and not their weight. But the input data will come from patients in the ED. 

They will rate their pain on a scale of 0-100 at the beginning and end of their visit. Barnhart says should this approach be superior to weight-based doses, it will be a highly effective way to treat pain in sickle cell disease in emergency departments.

Rare Eye Disease: Retinitis Pigmentosa

Treating rare diseases presents numerous challenges. For one, the population is small and scattered geographically. This is the situation for a rare eye disease called retinitis pigmentosa.

RP is an inherited disorder that affects light-sensing cells in the retina, leading to problems with vision, especially adjusting between light and dark. For some patients, the reason for the condition — genetic, of course — is the RLBP1 gene failing to make a protein that feeds the light-sensing photoreceptor cells. This can eventually lead to blindness. 

To try to treat this condition, the Novartis Institutes for BioMedical Research have developed an investigational gene therapy, which requires a normal RLBP1 gene to be inserted into the faulty cells. Kali Stasi, translational medicine director at Novartis, says the condition (RLBP1 RP) has no approved treatment, which is why this study is so important. Indeed, the gene therapy comes off the back of many years of investigational work. 

The Novartis team was motivated to take this experimental route after valuable evidence from studies with mice. Mice with inactive RLBP1 genes were given a single dose of treatment resulting in faster recovery from flashes of light, which has lasted a year after treatment.

If even some of the treatments highlighted in this post prove to be successful, patients could well be facing the heady prospects of a life that is free from illness. For others, the gains may be more subtle, such as simply being able to manage their pain better. Nevertheless, the quality of experimental treatments underway should be reason to be, even if only cautiously, very optimistic. 

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