Implementation of Dialyzable Leukocyte Extract to Treat Multiple Sclerosis: A Clinical Case

ABSTRACT

Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS) with its chronic inflammatory component. In the treatment of MS, corticosteroids are usually implemented to reduce the disease's inflammation rate. In this case study, we present a patient with MS that initially received corticosteroids, which heightened his vulnerability to infections, particularly respiratory ones. Consequently, the treatment was changed to the administration of dialyzable leukocyte extract (DLE) “Oral Transferon”. To this day, the rate of inflammation has been reduced, slowing the evolution of MS, decreasing the clinical manifestations of the disease, and improving the patient's quality of life. This may be attributed to the immunomodulatory effects of the Transferon. More studies are needed in MS patients implementing a treatment based solely on Transferon to establish its effectiveness as an immunomodulator (specifically for this autoimmune disease).

Patient's brain MRI with an intravenous contrast medium. (A) Multiple hyperintense immunomodulated demyelinating plaques are observed on axial plan T3 fluid‐attenuated inversion recovery in periventricular and juxtacortical, white matter. In (B), the same demyelinating plaques are observed after 11 years of treatment with oral Transferon.

Summary.

• This clinical case shows the implementation of dialyzable leukocyte extract “Oral Transferon” as the only treatment in a patient with multiple sclerosis (MS) which stopped the disease progression and reduced the clinical manifestations possibly due to its immunomodulatory effects.

1. Introduction

Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS) with its chronic inflammatory component; the triggering of the disease may be related to genetic predisposition, autoimmune, and environmental factors [1]. Today, the pathogenesis of MS is not completely understood but is associated with the activation of autoreactive lymphocytes that infiltrate the CNS and cause demyelination [2]. The signs and symptoms of MS vary depending on the severity and presentation of the disease; in the neurological examination of patients with longstanding disease, they mainly present hyperreflexia, spasticity, plantar response in extension, weakness, ataxia, loss of sensitivity, and visual and sphincter alterations. For some people, MS is characterized by periods of relapse and remission, while for others it has a progressive pattern [3, 4]. Here we present the implementation of low‐molecular‐weight peptides (< 10 kDa) derived from leukocyte lysates, which modulate the production of proinflammatory cytokines. According to Vallejo‐Castillo et al. [5], monomeric human ubiquitin (Ub) has been identified as the main peptide component of the DLE (Dialyzable Leukocyte Extract). These authors also suggest that Ub can activate its extracellular receptor (CXCR‐4) in the stomach, which causes systemic immunomodulatory effects through the vagus nerve. In fact, the DLE modulates the production of proinflammatory cytokines, including TNF‐α, IL‐6, and IFN‐γ [5, 6]. Oral Transferon, created by the National Polytechnic Institute in Mexico, is a dialyzable leukocyte extract (DLE), which is an immunomodulatory agent that is usually used as an aid in the treatment of inflammatory diseases [6, 7], but in this case, it has been used to treat a patient with MS.

2. Case Description

In 2007, a 27‐year‐old Mexican male with a chemical engineer occupation (stressful work activity) and no family history of autoimmune diseases reported muscle pain in the lower back. Days after the first symptoms, he presented sporadic visual impairments such as nystagmus and diplopia, followed by other disorders such as vertigo, paresthesia, muscle weakness, and fatigue. He started losing mobility in his lower limbs in 2012, and by 2013, he was experiencing slight spasms and difficulty performing activities but still retained some movement. At that time, the patient needed to use a cane as support when walking. Subsequently, the patient visited a neurologist, who made the diagnosis of advanced relapsing–remitting multiple sclerosis after a series of tests such as a dorsal column magnetic resonance imaging (MRI), which presented active demyelinating plaques in the spinal cord, an electroneuromyography (EMG), and a somatosensory evoked potential (SEP) of the tibial nerves (long latency) which revealed the presence of diffuse demyelination of both tracts. According to the updated McDonald criteria for MS diagnosis [8], an MRI presenting at least two active demyelinating plaques in the brain and/or spinal cord confirms MS. For that reason, oligoclonal bands (OCBs) and vasculitis tests were not considered because the previously mentioned tests were enough to confirm the diagnosis. From 2013 to date, the patient's treatment has solely relied on oral Transferon [5, 9]. In the first 6 months, the patient received an oral dose (2.0 mg/5 mL) for five continuous days, and subsequently a dose of 2.0 mg/5 mL every 3 days for 15 days. Finally, a dose of 2.0 mg/5 mL every week, for the remaining months. Afterward, the treatment changed to a dose of 2.0 mg/5 mL every 10 days until 2015. From 2015 to date, the patient has received a dose of 2.0 mg/5 mL every 15 days. This treatment has significantly improved the previously mentioned clinical manifestations, except for his motor capacity, as he now requires a wheelchair. Medical appointments are annual, and treatment will be stopped when his doctor indicates it.

3. Methods

In 2008, a lumbosacral spine (AP and lateral) x‐ray was performed, which presented a probable root compression at the levels of L4 and L5. A lumbar MRI in 2010 revealed disc protrusions. A blood count test in 2013 revealed elevated leukocytes. Also, a dorsal column MRI was performed, which revealed the presence of diffusely distributed signal hyperintensity throughout the entire spinal cord in relation to demyelinating plaques. In this same year, an EMG (Table 1) was performed to rule out myelitis. The parameters were normal, but mild irritation of the right S1 root was observed. The doctor indicated a SEP of the tibial nerves (long latency) to confirm the diagnosis of MS (Table 2). The SEP concluded with an abnormal result, confirming diffuse demyelination of both tracts. Advanced relapsing–remitting MS was diagnosed. Treatment with corticosteroids was started to reduce the disease's inflammation rate; subsequently, the patient began to present clinical manifestations of Cushing's syndrome which led to the treatment being suspended. Instead, an oral Transferon‐based treatment was implemented in the patient. Since 2013, the patient has only received oral Transferon treatment.

TABLE 1.

Results of electroneuromyography (EMG) of the case.

Nerve	Segment	Latency (ms) Distal/Proximal	Amplitude (mV) Distal/Proximal	Speed conduction	Distance (mm)	Result
Ulnar (right)	Forearm	2.9/7.2	10.6/7.3	60.50	260	Normal
Ulnar (left)	Forearm	3.6/8.0	7.0/5.6	54.50	240	Normal
Median (right)	Forearm	3.0/7.8	7.2/8.3	54.20	260	Normal
Median (left)	Forearm	3.1/7.5	8.1/5.7	61.40	270	Normal
Peroneal (right)	Leg	4.2/13.2	1.7/1.2	41.10	370	Low amplitude
Peroneal (left)	Leg	4.2/12.9	2.8/2.6	44.80	390	Low amplitude
Tibial (right)	Leg	4.0/13.2	12.9/12.2	44.60	410	Normal
Tibial (left)	Leg	4.0/13.6	10.7/10.9	42.70	410	Normal

Note: Regarding motor neuroconduction, the EMG showed normal bilateral ulnar, median, and tibial nerve potentials. Both peroneal nerves showed normal latencies and speed conduction but presented low amplitudes.

TABLE 2.

Results of the Somatosensory Evoked Potential (SEP) test of the case.

Tibial nerve	Right		Left
	Latency (ms)	Amplitude (μV)	Latency (ms)	Amplitude (μV)
P42	49.7	0.78	52.9	0.95
N50	60.5	0.49	63.4	0.14
P65	67.2	0.33	70.1	0.22
N86	89.6	1.77	89.5	1.57

Note: The SEP showed abnormal long‐latency tibial nerves, indicating diffuse demyelination in both pathways.

4. Results

After implementing oral Transferon for approximately a year, the patient demonstrated improvements in his motor skills (particularly hand mobility), the deterioration of his optic nerve stopped, he no longer showed progression of visual damage, the appearance of infectious episodes decreased, and most importantly, his quality of life improved. Currently, the patient is still following a treatment based solely on oral Transferon, which has improved the previously mentioned clinical manifestations. Although there have been improvements in the patient's motor ability, he still requires the use of a wheelchair. In 2021, an MRI showed several immunomodulated demyelinating plaques in the brain (Figure 1A, arrows). This suggested that the rate of inflammation had decreased, leaving only the disease's sequelae. The treatment based solely on oral Transferon stopped the disease progression and reduced the clinical manifestations possibly due to its immunomodulatory effects. The patient's immune and nervous systems have improved, indicating a halt to the disease's progression, as evidenced by a recently performed contrast‐enhanced MRI of the brain that shows the same demyelinating plaques seen in 2021 (Figure 1B, arrows).

FIGURE 1.

Patient's brain MRI  with an intravenous contrast medium. (A) Multiple hyperintense immunomodulated demyelinating plaques (arrows) are observed on axial plan T3 fluid‐attenuated inversion recovery (FLAIR) (MRI 1.5 T) in periventricular and juxtacortical, white matter. In (B), the same demyelinating plaques (arrows) are observed after 11 years of treatment with oral Transferon (axial plane T2, MRI 3 T). Both images were taken with a high‐field MRI, however, the range used is different. (A) 1.5 T and (B) 3 T. Therefore, the details are best observed in (B).

5. Discussion

Various authors have demonstrated the usefulness of Transferon (Transfer Factor) in the treatment of autoimmune diseases. Patients have used it as an adjuvant and therapeutic immunomodulator for allergic diseases like rhinitis, asthma, sinusitis, respiratory infections, and even for cancer treatments such as breast, cervical, prostate, and colon cancer [5, 10, 11, 12]. However, limited studies have demonstrated its effectiveness in treating autoimmune diseases such as MS. In this MS clinical case, the patient has been receiving oral Transferon exclusively since 2013, mainly due to the initial treatment with corticosteroids, which caused the patient to present symptoms of Cushing's syndrome, which disappeared after suspending the steroid treatment and replacing it with the sole use of oral Transferon. After that, the progression of the disease slowed, leaving only the sequelae. The patient has improved his motor skills (such as hand mobility), and the visual deterioration has decreased. Although there was damage to the left optic nerve, it has not progressed.

Human leukocytes are the source of the dialysis extract known as Transferon. It is composed of a complex mixture of peptides of low molecular mass (< 10 kDa) [9]. Patients use this blood‐derived product, known as oral Transferon or Transferon, to treat inflammatory diseases, affecting the production of proinflammatory cytokines and accelerating the healing of infectious diseases. However, it still lacks a full understanding of the molecular mechanisms behind these therapeutic effects, as it remains unclear how the same product can modulate Th1 or Th2 mechanisms depending on the illness [13]. The composition of dialyzable leukocyte extracts represents the immunomodulatory function since it contains regulatory molecules that limit sensitivities and allergies, as well as an inducing portion that strengthens the antigenic stimulation [14]. Multiple sclerosis is characterized by the appearance of sclerotic plaques caused by inflammatory damage to nervous tissue, which leads to its demyelination. Physicians should be aware that, regardless of the subtype of MS a patient suffers from, the course of the disease is unpredictable. The frequency, number, and severity of exacerbations are different for each patient, and physicians must understand the fear and anxiety that this uncertainty can cause in their patients. Unfortunately, in the clinical case reported here, there was no timely diagnosis, which contributed to the disease's progression and impacted in the patient's quality of life. On this matter, various authors point out that early recognition and accurate diagnosis of MS are crucial to delay the disease progression and thus reduce or regulate possible complications that can arise in patients. Furthermore, delaying treatment can lead to the accumulation of disability and complications, ultimately resulting in irreversible neurological damage. Different authors agree that physicians can make an early and accurate diagnosis of MS by looking at the patient's full medical history, using diagnostic criteria, doing imaging, and other diagnostic tests. Those suspected of having MS who cannot confirm their diagnosis through evaluation and analysis should consult a neurologist. This is because the lack of specific antibodies like IgG (immunoglobulin G) in OCBs [15, 16] may lead to a late diagnosis and subsequent progression of the disease, similar to the MS clinical case presented in this work. Some authors suggest detecting IgG in OCBs to measure its increase in CSF (cerebrospinal fluid), as its index becomes abnormal when there is an alteration in the immune system [8, 17]. They also suggest that two or more OCB tests are required to confirm a positive result. However, despite the OCBs test's high sensitivity to the inflammatory process, it lacks specificity for this disease. Therefore, a thorough clinical examination is crucial, as MS can be mistaken for other conditions like antiphospholipid syndrome, acute disseminated lupus erythematosus, Takayasu's disease, meningovascular syphilis, or even carotid dissection. Also, various infections, such as HTLV1 and Lyme disease, may present similarities with MS [18, 19]. According to the updated McDonald criteria for MS diagnosis [8], in most cases, an MRI revealing at least two active demyelinating plaques in the brain and/or spinal cord confirms MS [20].

By using specific treatments for MS, physicians can help patients prevent potential complications and slow the progression of the disease. Stress modulation, physiotherapy, and balanced diets to improve the quality and lifestyle of patients are also important factors in MS treatment, establishing that patient participation is critical for delaying disease progression [21]. Also, comorbidities are very frequent in patients with MS, which increases the risk of polypharmacy. A study conducted in Spain in 2023 by Santiago‐Perez et al. [22], which included 1407 patients with MS from 57 participating centers, showed that most patients resort to polypharmacy due to the presence of major comorbidities. Despite being treated with first‐line drugs (dimethyl fumarate and teriflunomide) or second‐line drugs (fingolimod and natalizumab), they needed to implement concomitant drugs, such as antihypertensives, antipsychotics, or antiepileptics, to alleviate manifestations associated with progression of the disease, like anxious‐depressive, cardiovascular or respiratory symptoms.

The relevance of this case is that the patient has been treated solely with oral Transferon, which shows that it may be a viable treatment option for patients with MS, since it stops the progression of the disease possibly due to its immunomodulatory effects by inhibiting the immune system from attacking the CNS, thus stopping the formation of demyelinating fibrotic plaques in the white matter. As a result, the immune and nervous systems and the patient's quality of life improved. Also, this treatment option has a lower cost compared to other drugs used to treat the disease. This case study shows that oral Transferon probably due to its immunomodulatory properties may effectively treat MS (specifically the relapsing–remitting type which the patient presented); however, more research is needed to confirm its effectiveness as a treatment for MS.

6. Conclusion

From 2013 to date, the patient has only received treatment based on Transferon in its oral form. To this day, the progression of the disease has stopped, leaving only sequelae. The patient has improved his motor skills (particularly hand mobility), and although there was damage to the left optic nerve, it has not progressed. This may be due to the implementation of oral Transferon, which could have been effective in reducing the rate of inflammation, slowing the evolution of MS, reducing the clinical manifestations of the disease, and improving the patient's quality of life. In addition, the recurrence of infections (particularly of the respiratory system) decreased, mainly due to having suspended the implementation of corticosteroids in the patient. More studies are needed in MS patients implementing a treatment based solely on Transferon to establish its effectiveness as an immunomodulator (specifically for this autoimmune disease).

Author Contributions

Layla Grecia González‐González: conceptualization, formal analysis, investigation, methodology, writing – original draft. Vicente Panameño‐Cruz: conceptualization, formal analysis, investigation, methodology, writing – original draft. Juan Pedro Luna‐Arias: formal analysis, validation, writing – review and editing. Elizabeth Reyna‐Beltrán: conceptualization, project administration, supervision, writing – original draft, writing – review and editing.

Consent

The patient provided written informed consent to publish this report, in line with the journal's patient consent policy.

Conflicts of Interest

We have no conflict or commercial interest in the development of this drug. The authors have no relationship with the National Polytechnic Institute, Mexico.

Data Availability Statement

All data underlying the results are available as part of the article and no additional source data are required.