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Guest article by Ingrid R Niesman, MS PhD
While we don’t really know the extent of pain cats actually experience, we do know that they are masters at masking their discomfort, leaving cat parents to guess. This is especially true with arthritis pain. Just like humans, cats’ joints endure a lifetime of abuse and show similar arthritic tendencies with age. Humans can avoid suffering with medications and joint replacements. Our cats with chronic osteoarthritis (OA) or degenerative joint disease (DJD) have fewer options.
A new option for controlling feline pain
In January of this year, the FDA approved the first feline-specific pain medication. Marketed by Zoetis under the trade name Solensia, this monthly injectable treatment is expected to arrive in veterinary clinics later this year. This can be a game-changer for many aging cats. Although there are two NSAIDs (non-steroidal anti-inflammatory drugs) approved for cats overseas, none are approved in the United States. NSAIDs in general are harsh on the kidneys, making them questionable choices for chronic use in felines, even though they are considered mildly safe.
What is Solensia and why is it different?
Solensia (frunevetmab) is a organic therapy, as opposed to common medications which are small molecule drugs. A organic is a protein or lipid molecule derived from natural sources. In the case of Solensia, this therapy is derived from a single rat hybridoma cell clone, what cell engineers call a monoclonal antibody.
Hybridoma cells are a fusion of two reactive immune cells; one that has been exposed to a specific reactive protein – in Solensia’s case, nerve growth factor (NGF); the other an antibody producing B cells. These fusion cells are then selected for the best antibody that “sees” the specific reactive protein, eg NGF, the target of Solensia.
To make this rat antibody safe for cats, the molecule had to be reconfigured into a typical feline antibody class, while leaving the part that could neutralize NGF intact. This fully feline anti-NGF monoclonal antibody is now Solensia.
How does Solensia work?
NGF has two opposing sides to its biological function. On the one hand, this protein is essential for the development of brain connections in infancy and for neuronal survival in infancy. But later in adulthood, NGF plays a modulating role in pain sensations, promoting stimulation rather than suppression of nerve endings.
In order to affect biological processes, a protein like NGF must first bind to another surface protein, enter a cell, be transported to a cell nucleus, and communicate that something must change in the current state of ‘a cell. Many drugs block, modify or reverse this delicate dance of cell signaling in one way or another. Solensia works by preventing NGF from binding to its membrane receptor – TrkA; and block cell entry. No signaling means no pain response from the neuron.
Osteoarthritis and DJD can lead to increased localized NGF. Cells that keep synovial fluid flowing and cartilage healthy are damaged as osteoarthritis progresses and pump out increasing amounts of NGF. Pain and discomfort ensue.
Will this be effective in treating my cat’s OA or DJD pain?
Effective pain control is one of the greatest enigmas of modern medicine. If a drug works, it can be addictive or lose its effectiveness over time. Given the biological role that NGF plays in modulating pain, considerable work has been devoted to the development of therapies that could block its action.
Unfortunately, early attempts to treat humans with anti-NGF therapies resulted in rapidly accelerating the progression of OA or DJD and damage to nerve endings, especially when combined with NSAIDs. The FDA halted all human clinical trials in 2010. Interest in renewed development arose when anti-NGF monoclonal antibodies were shown to have significant pain-reducing properties for osteoarthritis of the knee and hip in human trials.
The good news for cats is that in recent placebo-controlled proof-of-concept and safety clinical trials of Solensia, cats’ mobility improved over baseline activity, as reported by in-home questionnaires. . B. Duncan Lascelles, Ph.D, FRCVS, DACVS from the North Carolina State University College of Veterinary Medicine and investigator on three of the published Solensia trials, describes the results as dramatic. “In our initial trial, this was the first time I had seen clear beneficial pain reduction results. during the study. In studies of other therapies, we get our answer about the effectiveness of a therapy when we perform the data analysis; but in this study, we saw clear signs of pain reduction in patients over the course of the study. Customers have reported cats turning back into kittens…jumping backwards on counters. These same results were maintained in the next two larger trials. »
In addition to customer-reported results, investigators used accelerometry data (no, cats don’t wear iPhones!) to back up subjective data with precision measurements. Although all cats had some decrease in activity, there were considerable differences between the treated cats and the control cats.
What about the safety of my senior cat?
Arthritis of the hip and spine is primarily a disease of aging felines. So how will this therapy be tolerated by older cats? Published data describes a doubling of vomiting problems when cats are injected with Solensia. However, overall, cat parents were satisfied with the results on their cat’s response to treatment.
My main concern after reviewing the trials conducted in the United States and the European FDA summary is the lack of long-term monitoring for rapid joint degeneration. Rapidly progressive osteoarthritis (RPOA) is a known condition with an increased incidence in human anti-NGF monoclonal antibody trials, particularly when higher doses were given or NSAIDs were used concurrently. time. “Obviously we’re all aware of and watching for something similar in cats, but as far as I know the condition of RPOA has never been described in cats or dogs, and nothing similar has been seen in the Solensia studies,” said Dr. Lacelles. “This condition, RPOA, may be a unique human pathology.” Further data will be collected once Solensia becomes commercially available.
When asked about chronic use by cat clients, Dr. Lascelles brought up an interesting point. “Pain negatively affects the whole body, not just the localized site. But once we treat the pain, everything gets better – all parts of the body and the pain transmission system become more normal. Once this happens – once the pain is under control – the time between doses may be lengthened. We are already hearing reports about this from colleagues in the EU where the drug has been used clinically.
No daily pills
Giving a cat pills every day is daunting to most cat parents, even with treats that hide pills. Dr. Lascelles told me that he didn’t appreciate the burden associated with pilling a cat until he had to pill his own cats! An injection once a month is a tempting option. However, putting your cat in the carrier and getting to the vet can also be a hurdle for many.
With Solensia’s US approval and soon to be in veterinary clinics, now is a good time to assess the health of your aging cat. Do you see any signs of loss of mobility or reduced quality of life? If so, contact your veterinarian and discuss what a treatment plan with Solensia could do to improve overall health. Once my cats get to that point, I will ask the same questions.
Ingrid R. Niesman MS PhD is the director of the SDSU Electron Microscope Imaging Facility at San Diego State University. She graduated from Utah State University and earned her master’s degree from the University of Illinois-Urbana-Champaign. After 30 years of technical electron microscopy, cell biology, neuroscience and infectious disease research, Dr Niesman completed his PhD in the UK at the University of Sunderland. His work experience includes time at LSU Medical School, Washington University, UAMS in Little Rock, UCSD, TSRI and a postdoctoral year at CALIBR in La Jolla, CA. She has worked for at least two members of the National Academy of Science and is credited with over 50 publications. She can be reached at iniesmanphd@gmail.com
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