NEWS

Use of botulinum toxin mitigates effects of rare neurological disease

Application improves clinical condition of patients with spastic paraparesis

authorship
image editing

The use of botulinum toxin in patients with spastic paraparesis – drare hereditary disease that causes weakness and muscle spasms in the legs - can improve the fatigue and tiredness when walking. This is what a doctoral study from the Faculty of Medical Sciences (FCM) has indicated, with results that are still preliminary, but which are already showing promise for treating patients with this condition.

According to the study advisor, professor Marcondes Cavalcante França Jr., essthe toxin (popularly known as botox) is already used in other situations, but there was still no solid research addressing its application in spastic paraparesis. “It was not clear whether it would help with gait speed and in what aspects it would contribute”, he says, who is professor at FCM and neurologist at HC.

Fifty-five patients received botulinum toxin and placebo (saline) injections at the HC Neurology Outpatient Clinic. The study design was cross over, that is, the patient first received an injection of botulinum toxin and, secondly, a placebo (and vice versa). Everyone received at least one application of toxin and another of placebo, with an interval of four months between one administration and another. They were then evaluated.

In addition to the perception of fatigue and tiredness, a series of parameters were investigated. The study indicated that some patients significantly reduced their pain when administered botulinum toxin. Regarding gait speed, some patients also had a good result, becoming faster. Others, however, were not responsive to the intervention. For those who went, the idea is to continue research in this direction.

Photo: Antoninho Perri
Professor Marcondes Cavalcante Franla Jr.: “We have sought to develop new analysis tools to facilitate the interpretation of brain MRI” 

Nowadays, the treatment of choice is non-pharmacological. And all cases require physiotherapy and motor rehabilitation. Drug treatment is still limited. For spastic paraparesis, oral muscle relaxants are generally prescribed, such as baclofen and cyclobenzaprine. But in practice they have a discreet effect. “Systemic muscle relaxants sedate and cause drowsiness. Therefore, it is necessary to identify new treatments”, highlighted the neurologist.

Spastic paraparesis is a rare and underreported disease, he describes. There is no Brazilian data on the subject. European data suggest the occurrence of five to six cases for every 100 people. At the HC Neurology Outpatient Clinic, around 200 cases are being treated, from all over Brazil.


Evolution

Marcondes commented that degenerative diseases progress inexorably, and it is not possible to act on their progression. Most people with paraparesis suffer more from morbidity than mortality. Thus, morbidity greatly affects your quality of life: your long-term perspective.

In psychological terms, many of them deal with a perception of guilt, as it is a genetic disease transmitted to their children. Furthermore, these diseases also carry great social stigma. This is the case of ataxias, which interfere with motor coordination and balance. Some patients have already been turned away from restaurants because they thought they were drunk, lamented the neurologist.

Until recently, not much could be done for patients with degenerative conditions. “This has changed with the many new developments that have been achieved. Some even involve medicines already approved for clinical use or in the process of being approved”, informed Marcondes.

In much of the research to understand the disease mechanism that leads to the death of neurons, possible therapy targets have already been identified. Unicamp Neurology is participating in testing new medications. One is a multicenter clinical trial in ataxia. “We were the only center invited to participate in this research, outside the Europe and USA circuit, because we are a reference on the subject”, he reported. 

Approval has already been received from the Research Ethics Committee (CEP) and the process is now being processed by the National Commission for Ethics in Research (Conep). The expectation is that the studies will begin in the middle of this year, already having approval from the Food and Drug Administration (FDA).

Unicamp was also chosen for this trial because it has consistent production and a large number of patients. “We have sought to develop new analysis tools to facilitate the interpretation of brain MRI, for example. We have just created a tool for analyzing cervical cord images. The results have been very interesting, so much so that it is already being used outside the country”, explains the professor.

In the Neuroimaging Laboratory, through magnetic resonance imaging, quantitative analyzes are carried out and parameters such as volume of structures, cortex thickness and degree of integrity of white matter tracts are measured. This leads to greater exam accuracy, not just a visual analysis, an impression.

Open software was also developed that allows quantitative analysis of the cervical cord. The technique is already validated and has already generated a series of works. The intention, according to the professor, is to monitor patients with a more refined measure.

Another clinical trial on paraparesis will soon begin with a new drug for therapeutic use, produced by a Brazilian laboratory. It is a herbal medicine extracted from a medicinal plant and has a local effect, for topical use.

 

Practice

Marcondes coordinates the area of ​​neuromuscular and neurogenetic diseases at HC. He reports that these diseases have in common the fact that they interfere with patients' motor coordination. Along these lines, motor neuron diseases have been researched, which mainly include sclerosis amyotrophic lateral disease (ALS) and hereditary spastic paraplegias, in addition to ataxias, which essentially affect the cerebellum.

“We have tried to make an early diagnosis, as many diseases are difficult to decipher. We have also been looking for new techniques”, stated the advisor. “But, for these three groups of diseases, unfortunately there are no effective treatments to date. New paths need to be sought.”

Today, different approaches are taken using imaging techniques and markers that can be measured in peripheral blood and cerebrospinal fluid. A second front consists of understanding the mechanisms that these diseases have through different assessments. The third front involves exploring new treatments for patients in the short term.

Paraplegias, for example, have a genetic cause and lead to changes in the spinal cord. The patient develops weakness, loss of movement and hypertonia (stiffness) in the legs. Many are restricted to a wheelchair. This type of pathology mostly affects young adults. But when it affects children, it is more severe, as they are still in formation.

For this group of diseases, there is no well-established treatment or standardized research. The clinical trial, from an experimental point of view, would be the most robust way to verify the efficacy and safety of a given drug and a given disease.

All of these diseases evaluated are progressive and deserve a specific approach. ALS, which is the most prevalent in the Brazilian population, can lead to death in just two years. Its progression continues to be rapid and has a greater impact on the patient and family. Therefore, there is urgency in the development of research and innovation. Other degenerative diseases can take ten to 15 years to evolve.

Marcondes emphasized that research into rare diseases can serve as an important study model (in terms of disease mechanism and treatment) and can be extrapolated to other disorders. In spastic paraparesis, the symptoms are similar to those of those who have had trauma to the spinal cord. The site of injury is practically the same. Symptoms such as leg weakness are practically the same. What differs is the mechanism, which is degenerative due to trauma.

Assertive diagnosis, professional qualification, the search for adequate infrastructure and access to treatment are, together with new studies, new medications and new techniques, conditions that contribute to greatly improving the quality of life of patients with these diseases, believes the neurologist . 

 

JU-online cover image
Audio description: In the room, side image, man sitting in a chair on the left in the image, looking to the left, points with his left arm at the LCD monitor, touching the screen with his index finger, while keeping his right arm raised and touching the side of his stomach. In front of him, there is an L-shaped wooden table, on which is this monitor that displays eighteen small images of brains, grouped next to each other forming three rows. The images look like a tomography exam. Image 1 of 1

twitter_icofacebook_ico